Project Summary Virtual Cell (VCell) is a problem solving environment built on a central database and disseminated as a client-server application. It is designed to make mathematically sophisticated computational modeling and simulation accessible to cell biologists. The resource is open and free to the cell biology and scientific software developer communities. Currently, there are >6300 users who have built models and run simulations through the VCell servers, all saved in the VCell database. VCell supports a number of key biophysical mechanisms, including reaction kinetics, diffusion, flow, membrane transport, lateral membrane diffusion, electrophysiology and rule-based models of multi-state/multi-molecular interactions. Reaction-diffusion simulations can be based on 1D, 2D or 3D analytical or experimental image-based geometries. Users may choose among multiple available simulation approaches: ordinary differential equations, partial differential equations, stochastic reaction kinetics, network-free simulations, spatial particle- based simulations and spatial hybrid stochastic/deterministic simulations. A newly developed technology now allows for simulations of reaction diffusion equations in geometries with changing shape. The research needed to develop the existing VCell technology was developed over a period of 20 years. This grant application aims to preserve the availability of the large amount of data and unique functionality provided by the VCell platform for the scientific community. It will also provide the time to plan for a careful and deliberate transition to a self- sustaining financial model for the VCell resource.